Il semble que la voie de l’ADP soit particulièrement impliquée dans le profil plaquet- taire que nous observons après hémorragie méningée. Dans la méta analyse de la Cochrane de 2007 étudiant les traitements antiplaquettaires dans l’hémorragie méningée, 7 études ont été incluses, concernant 1385 patients. Les antiagrégants plaquettaires réduisaient le nombre de pronostic défavorable et d’ischémie retardée sans différence significative et aug- mentaient le nombre de complications hémorragiques. Deux limitations sont à apporter à ces constatations. Les patients de ces études avaient un traitement de leur anévrysme principalement par chirurgie et dans une bien moindre mesure par neuroradiologie in- terventionnelle. On peut raisonnablement penser que la neurochirurgie et l’adjonction d’un traitement antiagrégant plaquettaire puissent augmenter le risque de complications hémorragiques. D’autre part, quand les agents antiplaquettaires étaient étudiés individuel- lement, seule la ticlodipine était associée significativement à une diminution du nombre de patients avec un mauvais pronostic. La ticlodipine est un inhibiteur de la voie de l’ADP ce qui va dans le même sens que nos observations.
La milrinone n’a pas fait preuve de son efficacité dans l’HSA au travers d’une étude prospective, contrôlée. Néanmoins, plusieurs études ont montré son intérêt dans la prise en charge du vasospasme : Lannes et al. [60] rapporte 88 patients avec un vasospasme traité avec un protocole spécifique comprenant une perfusion de milrinone, 70% des patients avaient un bon outcome à 1 an avec un score de Rankin modifié <2, Fraticelli et al. [84] montre chez 22 patients une augmentation du calibre artériel après dilatation chimique par milrinone et un score de Rankin modifié<2 à 1 ans chez 18/22 patients. Le gain ap- porté par la milrinone est souvent considéré en lien avec son effet inotrope positif et son effet vasodilatateur. Un autre rôle de la milrinone qui pourrait être ajouté, ici, est son effet antiplaquettaire. En effet, certaines études[69, 90] ont montré un effet antiplaquettaire de la Milrinone : chez des adultes sains et des patients en post opératoire d’une chirurgie du genou, il existait un effet antiplaquettaire sur la voie de l’ADP et l’acide arachidonique qui était dose-dépendant. L’activation particulière à l’ADP dans l’hémorragie méningée pourrait expliquer une partie de l’efficacité de la Milrinone. Concernant notre population
de VS+, le traitement par milrinone IVSE pourrait avoir eu un double effet sur le va- sospasme et l’ischémie retardée : à la fois un effet vasodilatateur mais également un effet antiagrégant plaquettaire.
Dans le même ordre d’idée, la nimodipine donnée en prophylaxie chez les patients avec une HSA, ne diminue pas l’incidence du vasospasme mais améliore le pronostic, peut être en lien avec un effet antiplaquettaire. En effet, dans une étude randomisée[73] avec 41 patients recevant soit de la nimodipine, soit un placebo, le traitement par nimodipine n’avait pas proprement d’effet sur l’agrégabilité des plaquettes. En revanche, le relar- gage de thromboxane B2 augmentait significativement dans le groupe avec placebo alors qu’il restait stable dans le groupe nimodipine suggérant un effet antiplaquettaire de la nimodipine, pouvant jouer un rôle dans la diminution de l’ischémie cérébrale retardée et l’amélioration du pronostic.
Partie 5
Conclusion et perspectives
Nous avons confirmé l’hyperactivation et l’hyperagrégabilité des plaquettes dans des échantillons sanguins de patients après une HSA anévrismale alors que tous étaient traités par la méthode endovasculaire. La voie d’activation des plaquettes de l’ADP était parti- culièrement stimulable.
Le profil plaquettaire se modifiait au cours de temps avec une agrégabilité qui se ma- jorait alors que l’expression des molécules membranaires associées à l’activation tendait à diminuer. Chez les patients qui présentaient un vasospasme, l’activation endothéliale, explorée par le FVIII et le FvW, était particulièrement élevée en comparaison des patients n’ayant pas de vasospasme. Lorsqu’on comparait les patients avec HSA au patient de chi- rurgie orthopédique dont le statut thrombotique est reconnu, le profil d’activation était similaire, alors qu’ils n’avaient pas eu d’intervention chirurgicale. Ces résultats obtenus sur une petite cohorte de patients soulignent l’intérêt de considérer l’impact de la fonction plaquettaire dans l’HSA, en particulier lors des procédures endovasculaires à haut risque thrombotique effectuées pour le traitement initial ou le vasospasme.
Les traitements inhibiteurs de la fonction plaquettaire pourraient être proposés pour la prévention des lésions vasculaires associées au vasospasme après la prise en compte du risque hémorragique individuel. Le timing de ces traitements, durant l’artériographie, en dose unique ou dans les suites selon la durée de vie des agents utilisés, mériterait alors d’être étudié.
L’étude des concentrations circulantes de facteurs endothéliaux, tels que le FVIII et le FvW, pourrait avoir un intérêt dans l’évaluation du risque de vasospasme et son évolution dans le temps.
Si la prédiction du vasospasme et de l’ischémie retardée est un enjeu important, les traitements à proposer pour traiter le vasospasme ou la découverte d’une prophylaxie chez les patients les plus à risque sont un défi majeur dans cette pathologie.
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